The present invention relates to a monovalent H5N1 vaccine. More specifically, the present invention relates to the development of a monovalent H5 vaccine strain using hemagglutinin (HA) engineering to elicit cross-clade protection. The present invention also relates to an epitope-chimeric H5 and to a reverse genetics (RG) influenza virus expressing the epitope-chimeric H5.
The publications and other materials used herein to illuminate the background of the invention or provide additional details respecting the practice, are incorporated by reference, and for convenience are respectively grouped in the Bibliography.
Recurrence of highly pathogenic avian influenza (HPAI) virus subtype H5N1 in humans and poultry continues to be a serious concern to public health. Since their emergence in Asia over a decade ago, highly pathogenic avian influenza H5N1 viruses have spread to over sixty countries on three continents and are endemic among poultry in South East Asia and Africa (Peiris et al., 2007). It has caused disease in several mammals, including humans, often with lethal consequence. Up to date, H5N1 has resulted in 641 human cases worldwide, including 380 deaths (http, 2013). Although so far no sustained human to human transmission of the virus has been observed, the concern remains that, if human transmissibility was acquired, a severe pandemic could result (Guan et al., 2004; Imai et al., 2012).
Vaccination remains the most effective and economically prudent strategy to combat the threat posed by avian influenza viruses with pandemic potential (Baz et al. 2013). However, it will be a challenge to produce an effective vaccine if a pandemic comes up suddenly and spreads rapidly. Therefore, efforts are being undertaken to develop pandemic vaccines that use less antigen and induce cross-protective responses. The highly conserved ion channel protein (M2) (Wu et al., 2007) and the nucleoprotein (NP) of influenza virus have been evaluated for the induction of cross-protective cellular immunity and viral clearance (Chen and Subbarao, 2009). However, antibodies specific to these proteins are poorly immunogenic and infection permissive. Thus, the development of a vaccine based on influenza virus hemagglutinin (HA), the principal determinant of immunity to influenza virus, remains to be the most favorable option to prevent infections by HPAI influenza viruses (Gambotto et al., 2008). H5N1 viruses are antigenically distinguishable owing to differences in hemagglutinin sequences, resulting in different lineages or clades of H5N1 (Aubin et al., 2005; WHO et al., 2008). Due to variations in the HA sequences, particularly within the neutralizing epitope region, conventional HA based H5N1 vaccines appear not to be effective against heterologous strains or phylogenetically variant clades of H5N1 (Shore et al., 2013). Hence, the strategy to exploit a cocktail of antigenically different triple or more virus strains was developed to elicit broad protection. However, either the propagation of individual vaccine seed viruses or the development of co-expression recombinant vaccines is time-consuming, technique-demanding and expensive.
Therefore, it is important to develop a prepandemic monovalent vaccine that induces cross-clade protection against antigenically distinct H5N1 strains.